Table 3

Drugs for treating type 2 diabetes in adults (not including insulin or insulin analogs) but not yet approved in youth except for metformin

Drug classAvailable drugs in this classMechanism of actionSignificant adverse effectsApproved in patients <18 years old
Biguanides
  • Metformin

Decreases insulin resistance; reduces hepatic glucose production; increases peripheral glucose uptake; decreases gastrointestinal absorption of glucose
  • Gastrointestinal

  • Lactic acidosis

Yes
Sulfonylureas
  • Glipizide

  • Glimepiride

  • Glyburide

Stimulates secretion of insulin from the β-cell
  • Hypoglycemia

  • Weight gain

No
Meglitinides
  • Repaglinide

  • Nateglinide

Stimulates glucose-dependent secretion of insulin from the β-cell
  • Hypoglycemia

  • URI

  • Diarrhea

  • Headache

No
α-Glucosidase inhibitors
  • Acarbose

  • Miglitol

Delays absorption of glucose by intestines by inhibiting breakdown of complex sugars
  • Flatulence

  • Diarrhea

  • Abdominal cramps

No
GLP-1 agonists
  • Exenatide

  • Liraglutide

  • Dulaglutide

  • Lixisenatide

  • Albiglutide

  • Semaglutide

Incretin effect; slows gastric emptying; enhances postprandial insulin biosynthesis; improves β-cell function; decreases appetite
  • Acute pancreatitis

  • C-cell hyperplasia/ medullary thyroid carcinoma

  • Nausea/vomiting

  • Hypoglycemia

  • Diarrhea

  • Headache

No
DPP-4 inhibitors
  • Saxagliptin Sitagliptin

  • Alogliptin

  • Linagliptin

Inhibits DPP-4 enzyme, reducing endogenous GLP-1 breakdown
  • Acute pancreatitis

  • URI

  • UTI

  • Nasopharyngitis

  • Headache

No
Amylin analog
  • Pramlintide

Inhibits postprandial glucagon secretion; delays gastric emptying; improves satiety
  • Hypoglycemia

  • Nausea

  • Anorexia

  • Abdominal pain

No
Thiazolidinediones
  • Rosiglitazone

  • Pioglitazone

PPAR-γ inhibitor; increases insulin sensitivity in liver, muscle, and adipose tissue; decreases hepatic glucose output
  • Edema

  • Weight gain

  • Anemia

  • Elevated liver enzymes

No
SGLT-2 inhibitors
  • Canagliflozin

  • Dapagliflozin

  • Empagliflozin

  • Ertugliflozin

Allows more glucose to be excreted in the urine and hence lowers blood glucose
  • Euglycemic ketoacidosis

  • UTI

  • Candidal vulvovaginitis

No
Bile acid sequestrant
  • Colesevelam

Mechanism for glucose lowering is unknown
  • Gastrointestinal (gas, nausea, diarrhea, abdominal pain)

  • Weakness

  • Muscle pain

No
Dopamine-2 agonist
  • Bromocriptine (quick release)

Modulates hypothalamic regulation of metabolism; increases insulin sensitivity
  • Nausea/vomiting

  • Fatigue

  • Dizziness

  • Headache

No
  • DPP-4, dipeptidyl peptidase 4; GLP-1, glucagon-like peptide 1; PPAR, peroxisome proliferator–activated receptor; SGLT2, sodium–glucose cotransporter 2; URI, upper respiratory infection; UTI, urinary tract infection.